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Semiconductor nanowire devices are an exciting class of materials for biomedical and electrophysiology applications, with current studies primarily delivering substrate bound devices through mechanical abrasion or electroporation. However, the ability to distribute these devices in a drug-like fashion is an important step in developing next-generation active therapeutic devices. In this work, we will discuss the interaction of label free Silicon nanowires (SiNWs) with cellular systems, showing that they can be internalized in multiple cell lines, and undergo an active 'burst-like' transport process. The first portion of this work will be primarily focused on examining the interface between SiNWs and biological systems and on exploring the cellular mechanism of nanowire internalization. In specific, this work will start with a general introduction into working with nanomaterials at the interface with biology, and into cellular endocytosis processes. From here, we will demonstrate that SiNWs can be internalized, discussing a new microscopy technique, Scatter Enhanced Phase Contrast (SEPC) for visualizing SiNW/cell interactions, before showing how this technique can be used for tracking individual nanowire dynamics. Next, we will discuss SiNW internalization on the ensemble level, and show how this information can be used to explore the specific mechanism of endocytosis; concluding that SiNWs are primarily internalized through a phagocytosis process. This will be followed by a brief dialogue on how the route of endocytosis can be used to inform future device design. In the second portion of this manuscript, we will explore the use of SiNWs as independent diagnostic devices, showing that SiNWs with a kinked morphology can be used as inter- and intracellular force for extended continuous monitoring. This section will include a brief interlude into Euler-Bernoulli beam theory, describing the governing principle behind these force probes, before demonstrating their use in cellular systems. From here, we investigate force transduction dynamics, showing that the cell's cytoskeleton plays an important role in imparting force to the internalized devices. During the course of this investigation, it became clear that nanowire diameter plays a critical role in analyzing force probe device performance. To address this problem, we will conclude with a method for precisely calibrating intracellular nanowire diameter, using an optical to electron microscopy (EM) mapping function. In this process, we will study the interaction of light with silicon nanomaterials using Lorentz-Mie theory, to describe the range over which the optical transform is possible. Collectively, this work represents one of the first dynamic studies of semiconductor nanowire internalization and offers valuable insight into designing devices for bio-molecule delivery, intracellular sensing and photoresponsive therapies.


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